title: Tea polyphenol (-)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells.
abstract: METHODS
  The aim of this research was to explore whether the tea-polyphenol (-)-epigallocatechin-3-gallate (EGCG) could be used as a potential agent for blocking smoking (nicotine, Nic)- or hormone (estradiol, E2)-induced breast cancer cell proliferation through inhibition of a common signaling pathway.
  
  
  RESULTS
  To explore whether Nic (>0.1 μM, 24 h) and E2 (>1 nM, 24 h) significantly increased α9-nicotinic acetylcholine (α9-nicotinic acetylcholine receptor (nAChR)) mRNA and protein expression levels, real-time PCR and immunoblotting analysis experiments were performed in human breast cancer (MCF-7) cells. Luciferase promoter activity experiment was performed to test the α9-nAChR promoter activity affected by Nic, E2 or EGCG. The results indicate that treatment with EGCG (1 μM) profoundly decreases Nic- and E2-induced MCF-7 proliferation by down regulating α9-nAChR expression. The α9-nAChR promoter activity is significantly induced by 24-h treatment with Nic (10 μM) or E2 (10 nM) (>1.8 and ∼2.3-fold, respectively) in MCF-7 cells. Pretreatment with EGCG eliminated the Nic- and E2-induced α9-nAChR promoter-dependent luciferase activity. We further demonstrate that combined treatment with EGCG profoundly inhibits [3H]-Nic/ α9-nAChR binding activity in breast cancer cells.
  
  
  CONCLUSIONS
  We found that the EGCG could be used as an agent for blocking smoking (Nic)- or hormone (E2)-induced breast cancer cell proliferation by inhibiting of α9-nAChR signaling pathway. This study reveals the novel antitumor mechanisms of EGCG, and these results may have significant applications for chemopreventive purposes in human breast cancer.
authors.affiliation: Department of Surgery, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Tu
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Ku
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Ching-Shyang
authors.initials: CS
authors.lastname: Chen
authors.forename: Ching-Shui
authors.initials: CS
authors.lastname: Huang
authors.forename: Chia-Hwa
authors.initials: CH
authors.lastname: Lee
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chen
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Chien-Hsi
authors.initials: CH
authors.lastname: Chang
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004967:Estrogens; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009538:Nicotine / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction; D013662:Tea / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D005419:Flavonoids; D018733:Nicotinic Antagonists; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D013662:Tea; C443079:nAChR alpha9; D009538:Nicotine; D002392:Catechin; C045651:epigallocatechin gallate